Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency
- Yale University, United States
- NIH, United States
- Chinese Institute for Brain Research, China
- Peiking University, China
- Yale University School of Medicine, United States
Abstract
The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and nucleus basalis of Meynert (NBM) cholinergic terminal activity in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the cue-reward contingency. BLA CaMKIIα neuron activity followed reward retrieval and moved to the reward-predictive cue after task acquisition. Optical stimulation of cholinergic NBM-BLA terminal fibers led to quicker acquisition of the cue-reward contingency. These results indicate BLA ACh signaling carries important information about salient events in cue-reward learning and provides a framework for understanding how ACh signaling contributes to shaping BLA responses to emotional stimuli.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all experiments on Dryad Digital Repository: doi:10.5061/dryad.3xsj3txcf
-
Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingencyDryad Digital Repository, doi:10.5061/dryad.3xsj3txcf.
Article and author information
Author details
Rufina Kamaletdinova
Prithviraj Rajebhosale
Marina R Picciotto
Funding
National Institute on Drug Abuse (DA14241)
- Richard B Crouse
- Kristen Kim
- Hannah M Batchelor
- Rufina Kamaletdinova
- Justin Chan
- Steven T Pittenger
- Yann S Mineur
- Marina R Picciotto
National Institute on Drug Abuse (DA037566)
- Richard B Crouse
- Kristen Kim
- Hannah M Batchelor
- Rufina Kamaletdinova
- Justin Chan
- Steven T Pittenger
- Yann S Mineur
- Marina R Picciotto
National Institute of Mental Health (MH077681)
- Richard B Crouse
- Kristen Kim
- Hannah M Batchelor
- Rufina Kamaletdinova
- Justin Chan
- Steven T Pittenger
- Yann S Mineur
- Marina R Picciotto
National Institute of Neurological Disorders and Stroke (NS022061)
- Prithviraj Rajebhosale
- Lorna W Role
- David A Talmage
National Institute of Mental Health (MH109104)
- Prithviraj Rajebhosale
- Lorna W Role
- David A Talmage
National Institute on Drug Abuse (DA046160)
- Xiao-Bing Gao
National Institute of Neurological Disorders and Stroke (Intramural)
- Prithviraj Rajebhosale
- Lorna W Role
National Institute of Mental Health (Intramural)
- Prithviraj Rajebhosale
- David A Talmage
National Institute of Neurological Disorders and Stroke (T32-NS007224)
- Richard B Crouse
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were approved by the Yale University Institutional Animal Care & Use Committee in compliance with the National Institute of Health's Guide for the Care and Use of Laboratory Animals. (protocol: 2019-07895)
Reviewing Editor
- Matthew N Hill, University of Calgary, Canada
Version history
- Received: March 27, 2020
- Accepted: September 17, 2020
- Accepted Manuscript published: September 18, 2020 (version 1)
- Accepted Manuscript updated: September 22, 2020 (version 2)
- Version of Record published: October 1, 2020 (version 3)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 6,250
- Page views
-
- 760
- Downloads
-
- 33
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency
eLife 9:e57335.
https://doi.org/10.7554/eLife.57335
Further reading
-
- Computational and Systems Biology
- Neuroscience
The cerebellar granule cell layer has inspired numerous theoretical models of neural representations that support learned behaviors, beginning with the work of Marr and Albus. In these models, granule cells form a sparse, combinatorial encoding of diverse sensorimotor inputs. Such sparse representations are optimal for learning to discriminate random stimuli. However, recent observations of dense, low-dimensional activity across granule cells have called into question the role of sparse coding in these neurons. Here, we generalize theories of cerebellar learning to determine the optimal granule cell representation for tasks beyond random stimulus discrimination, including continuous input-output transformations as required for smooth motor control. We show that for such tasks, the optimal granule cell representation is substantially denser than predicted by classical theories. Our results provide a general theory of learning in cerebellum-like systems and suggest that optimal cerebellar representations are task-dependent.
-
- Neuroscience
The preBötzinger Complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases.
